Acute megakaryoblastic leukaemia (AMKL) in children: a comparison of AMKL with and without Down syndrome

Abstract

SummaryTo characterize childhood acute megakaryoblastic leukaemia (AMKL), we reviewed 45 children with AMKL diagnosed between 1986 and 2005 at Nagoya University Hospital and Japanese Red Cross Nagoya First Hospital. Twenty-four patients (53%) had AMKL associated with Down syndrome (DS-AMKL) and 21 (47%) had non-DS-AMKL. The median age of the DS-AMKL patients was 21 months (range, 8-38 months) and that of non-DS-AMKL patients was 15 months (range, 2-185 months). The morphology of blast cells was categorized into three groups according to the stage of megakaryocyte maturation. The blast cells were more immature in DS-AMKL than in non-DS-AMKL in terms of morphology and immunophenotyping. Cytogenetic abnormalities of leukaemic cells were classified into seven categories: normal karyotype including constitutional trisomy 21 in DS-AMKL; numerical abnormalities only; t(1;22)(p13;q13); 3q21q26 abnormalities; t(16;21)(p11;q22); )5/del(5q) and/or )7/del(7q); and other structural changes. The outcome of children with either DS-AMKL or non-DS-AMKL is excellent. The 10-year overall survival estimate was 79% [95% confidence interval (CI): 54-90] for DS-AMKL and 76% (95% CI: 58-91) for non-DS-AMKL (P = 0AE81) with a median follow-up of 78 months (range, 20-243 months). Our study shows the diverse heterogeneity of childhood AMKL and the need for subclassification according to cytogenetic and morphological features.

Acute Megakaryoblastic Leukemia in Children: Diagnosis and Management Challenges in Resource-Poor Countries

“…The median age at diagnosis was 1 year, which was lower than that in the total group of children with AML (13 years) and also lower than what is reported in literature [6,8,11].…”

“…The incidence of AMKL varies between 7.1 and 19.1% of AML cases in children [3,[6][7][8]. Recently, Hama et al have reported much higher incidence of AMKL at 23.2% in Japan [11]. This may indicate that the reported incidence of AMKL in our series may be an underestimation probably due to the difficulties of diagnosis.…”

“…The remission rate is approximately 96% with overall and event-free survival (EFS) of 79% [11]. Unfortunately, death of the female with DS was due to the treatment toxicity.…”

“…Acute megakaryoblastic leukemia is the most frequent type of AML in children with DS, and its prognosis is excellent in this group of patients with less intensive chemotherapy [4,5,11]. The remission rate is approximately 96% with overall and event-free survival (EFS) of 79% [11].…”

Leukemogenesis in Down syndrome

“…Similar cases are also observed in cells carrying trisomy 21 in mosaic models [12], suggesting that a cell-autonomous program provoked by the GATA1 mutation and trisomy 21 contributes to the onset of TAM. Relatively few cases of AMKL harboring mutations in the GATA1 gene exist in the absence of trisomy 21 [13,14]. Therefore, the pathogenesis of TAM seems to be closely associated with GATA1 dysfunction in combination with the impact provided by the extra chromosome 21.…”